Integrated Metabolism Flashcards
Since ATP is at the center of metabolism, what is the difference between anabolic metabolic process and catabolic oxidation process?
Catabolic leads to the production and release of ATP
Anabolic processes consumes ATP
What are the key metabolites and what junction do they meet at?
Amino acids, glucose and glycerol+fatty acids; meet at pyruvate
Where do key metabolites come from?
protein, carbohydrates and fat (dietary intake)
What are the excretory waste products produced from key metabolites?
Urea from Amino acids and water/carbon dioxide from citric acid cycle
There must be a balance of catabolism vs. anabolism in the body. What can the body do with blood glucose?
Use it, store it or convert it
What are the key metabolic players?
glucose-6-phosphate, pyruvate and acetyl-CoA
What main metabolic pathways use Glucose-6-phosphate?
glyconeogenesis, glycogenolysis, glycolysis and pentose phosphate pathway
Which metabolite has a negative allosteric effect on phosphofructokinase-1?
ATP; high concentrations will inhibit
What will happen to G6-P if phosphofructosekinase-1 is inhibited?
Concentration will increase
What enzyme will be stimulated at high levels of G6-P? What enzyme will be inhibited?
glycogen synthase leading to the formation of glycogen
inhibits glycogen phosphorylase thereby inhibiting glycogenolysis (glycogen degradation)
When there are high levels of NADP+ and low levels of NADPH, what does G6-P do?
It is used in the pentose phosphate pathway to produce NADPH
When there are low levels of NADP+ and high levels of NADPH, what does G6-P do?
PPP will not operate regardless of the concrentration of G6-P
How do the two isomers, Fructose-2,6-bisphosphate and Fructose-1,6-bisphosphate interact?
Abundance of F-1,6,-BP leads to a higher concentration of F-2,6-BP which in turn stimulates phosphofructokinase-1 ; this is known as feed forward stimulation
When there are high levels of glucose in the body, what hormone control is implemented and what is the result?
beta cells in the pancreas release insulin
decrease glucagon by increasing glycogen synthase and decreasing glycogen phosphorylase activity
When there are low levels of glucose in the body, what hormone control is implemented and what is the result?
pancreas releases glucagon–>liver G-protein–>cAMP–>phosphorylates glycogen synthase (no glycogen synthesis) and dephosphorylates glycogen phosphorylase (glycogenolysis)
What is the second major branch point in metabolism?
pyruvate
In low levels of energy (NADH not ATP) what enzyme is inhibited and how does it effect pyruvate?
pyruvate dehydrogenase kinase (PDK) is inhibited which keeps pyruvate dehydrogenase active. Leads to pyruvate is oxidatively decarboxylated to acetyl-CoA
What happens to pyruvate when there is high levels of NADH and Acetyl-CoA?
pyruvate dehydrogenase kinase is activated (turns off pyruvate dehydrogenase and Citric Acid Cycle)
If you have high concentration of ATP and Acetyl-CoA what happens to pyruvate carboxylase?
Pyruvate carboxylase is stimulated which is the first step of gluconeogensis as alternative pathway
How does pyruvate play a role in skeletal muscles if delta G is negative? What is the reaction and product and is it favorable?
In low levels of oxygen and anaerobic respiration, pyruvate combines with NADH and Hydrogen ion by the enzyme lactate dehydrogenase to produce lactate or lactic acid. The reaction is favorable since delta G is negative
How is lactate dehydrogenase stimulated under anaerobic conditions?
high levels of NADH
What is the Cori Cycle? (aka Lactic Acid Cycle)
in the liver, lactate can be converted back to glucose for energy production
What happens when there is a high concentration of lactic acid buildup in skeletal muscle and what is the signal?
inhibition blocks further conversion of pyruvate to lactate; burning sensation in muscles sends the signal
In the muscle, what enzyme converts pyruvate to alanine?
Alanine transaminase
What is the Alanine Cycle?
converts alanine back to pyruvate and glucose (gluconeogenesis) in the LIVER
Once oxygen levels are restored in skeletal muscles, what can resume?
ATP production via CAC/oxidative phosphorylation
What is the third primary branch point of metabolic control?
Acetyl-CoA
When there is too much energy, (high NADH/NAD+ ratio), what happens?
NADH inhibits the CAC via isocitrate dehydrogenase and alpha ketglutarate dehydrogenase
FADH2 causes increase in succinyl-CoA that slows down the CAC
In a fed state, how can the liver use acetyl-CoA?
make cholesterol, and/or Fatty acids / tricyglycerols;
increase in oxaloacetate condenses with acetyl-CoA producing citrate; increased citrate is transported to cytoplasm for FA synthesis and activates acetyl-CoA carboxylase and inhibits phosphofructokinase-1 (blocks glycolysis); G6-P that is blocked from glycolysis can be used to make glycogen or sent to PPP for make NADPH for FA synthesis
During starvation, what happens to acetyl-CoA?
FA oxidation supplies energy for gluconeogenesis;
increase in acetyl-CoA from oxidation of FA stimulates pyruvate carboxylase to promote gluconeogenesis
What does low levels of citrate and ATP/NADH/FADH2 promote?
Active CAC and oxidative phosphorylation
Which hormones stimulate glucose production in the liver when blood glucose is low and which hormones inhibit glucose use in muscle and adipose tissue?
Glucagon, catecholamines, cortisol and growth hormone stimulate liver
Cortisol and growth hormone inhibit glucose use
Which hormone inhibits liver glucose production and stimulates glucose use in muscle and adipose tissue when blood glucose levels are high?
Insulin
What is the process to form active insulin?
Prepoinsulin leader sequence removed forming proinsulin. Cleavage of the C-peptide will produce the the active form of insulin
If there is any metabolic pathway that produces glucose, how will insulin effect it?
Insulin will not stimulate any metabolic pathway that produces glucose or carbohydrate.
What is the process of insulin being released from Beta Cells in the pancreas when glucose levels are high?
Glucose enters the beta cells via the glucose transporter 2 (passive transport)
Glucose oxidation increases ATP levels and stimulated potassium channels
Depolarization opens voltage gated calcium channels to be released from the endoplasmic reticulum
Increase of intercellular calcium levels triggers release of insulin
Glucagon is a hormone that is released from alpha cells in the pancreas when glucose levels are low. What does the release of glucagon stimulate?
Acts mainly on liver stimulating glycogenolysis, gluconeogenesis, and FA oxidation
Glucagon can also stimulate the release of insulin allowing insulin-sensitive cells to take up the released glucose
Define catecholamines? What are they duel-hatted as?
They can acts as a neurotransmitter or hormone depending on the body’s needs
They are hormones (norepinephrine and epinephrine) that can provide immediate regulation of metabolism. Stimulates glycogenolysis and glycolysis for production of ATP in the muscle and inhibit glycolysis in the liver to provide glucose for the blood
Which metabolic pathways and location are stimulated by insulin?
Liver (gluconeogenesis, glycogenolysis)
Adipose tissue (Lipolysis)
Skeletal Muscle (glycolysis, glycogenolysis, and triglyceride uptake from lipoproteins)
What is Cortisol and what does it stimulate?
Cortisol is a chronic stress hormone that regulates metabolism
Stimulates corticotropin-releasing factor and adrenocorticotropic hormone.
Released from the adrenal glands
What is Diabetes Mellitus Type I?
No insulin is made at all (usually skinny people)
Result of autoimmune destruction of beta cells which leads to loss of insulin production
Without insulin, gluconeogenesis runs wild increasing blood glucose levels. Muscle and fat cells cannot take up available blood glucose via GLUT4 and the body can’t clear the elevated levels
Leads to increase lipolysis which increases ketone bodies (toxic) which leads to KETOACIDOSIS
What is Diabetes Mellitus Type II?
Insulin is produced but tissues are resistant to its effects (usually in fat people)
Results in uncontrolled gluconeogenesis which increases blood glucose levels even with high amount of insulin present
Ketoacidosis is not common
Leads to hyperosmolar hyperglycemia nonketotic syndrome (body tries to get rid of excess sugar by passing it into the urine)
